TrainerQ8_Layout 1 27/08/2009 16:56 Page 51
Pituitary Disorders
Advances in Our Understanding of Acromegaly –
Is There an Optimal Management Regimen?
Claire E Higham
1
and Peter J Trainer
2
1. Diabetes and Endocrinology Specialist Registrar; 2. Consultant Endocrinologist, Department of Endocrinology, Christie Hospital, Manchester
Abstract
The two- to three-fold increased mortality associated with active acromegaly can be significantly decreased and even normalised with
effective treatment to reduce growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels to within normal limits. This article
addresses the advances in surgical techniques, new approaches in radiotherapy and the choice of medical treatments that make it possible
to achieve biochemical remission and improve signs and symptoms of disease in almost every patient with acromegaly. The literature is
reviewed with regard to the relative merits of each treatment method, recent controversies such as the role of radiotherapy and primary
octreotide therapy are discussed and a treatment algorithm is proposed to provide a guide to management.
Keywords
Acromegaly, trans-sphenoidal surgery, radiotherapy, dopamine agonist, somatostatin analogue, pegvisomant, treatment algorithm
Disclosure: Claire E Higham has no conflicts of interest to declare. Peter J Trainer has received research support from Pfizer, Ipsen, Novartis and Novo Nordisk.
Received: 6 May 2009 Accepted: 16 July 2009
Correspondence: Claire E Higham, Department of Endocrinology, Christie Hospital, Manchester, M20 4BX, UK. E: cehigham@doctors.org.uk
Active acromegaly is associated with a two- to three-fold increase in surgical management is performed in a dedicated regional centre with
mortality that can be reduced to that of the background population small numbers of surgeons operating on a sufficient caseload to
with effective treatment to decrease growth hormone (GH) and maintain expertise. Other determinants of surgical outcomes are
insulin-like growth factor-I (IGF-I) levels to within normal limits.
1
tumour characteristics such as size, local invasion and extrasellar
Advances in surgical techniques, new approaches in radiotherapy and extension.
2
Large macroadenomas with extension into surrounding
a choice of medical treatments make it possible to achieve tissues are very unlikely to be amenable to surgical cure, and it has
biochemical remission in almost every patient with acromegaly. been argued that such patients would be better served by avoiding the
However, controversy persists around the optimal order and risks of surgery, such as hypopituitarism, and receiving a somatostatin
combination of modalities to achieve control of GH and IGF-I while at analogue (SSA) as first-line treatment. The combination of the
the same time relieving symptoms and preserving pituitary function. recognition that some macroadenomas cannot be surgically cured
In particular, the place of surgery as first-line treatment has been and the variable standards of surgeons have been the major forces
challenged by increasing interest and evidence that primary medical driving the interest in primary medical therapy with SSAs.
therapy can bring disease control without risking hypopituitarism and
the other complications of surgery. Radiotherapy
Radiotherapy treatment is effective at controlling GH secretion and
Surgery tumour growth, with up to 80% of patients achieving a GH <5mU/l at
Even with the increasing popularity of primary medical therapy, the 15 years.
6
Historically, in the UK fractionated three-field external-beam
majority of patients with acromegaly will undergo trans-sphenoidal radiotherapy at a dose of 4,500cGy was used as second-line adjunctive
surgery (TSS) as it offers the prospect of rapid, cost-effective therapy in patients with acromegaly not cured by surgery. However, it
correction of tumour mass effect and elevated circulating GH levels. has fallen out of favour principally because of concerns about the
The results of surgery continue to improve as a consequence of consequences of hypopituitarism and evidence of an increased risk of
innovations such as the endoscope and intra-operative imaging. In the a cerebrovascular accident (CVA).
7
Stereotactic radiotherapy in the
most successful series, 70–80%
2,3
of patients achieve remission; form of proton beam, Linac or Gamma Knife
©
are developing as
however, the success of surgery is operator-dependent and techniques for focusing high-dose radiation to well-defined residual
unfortunately, as most patients are operated on by less experienced tumour volume in a single session, while minimising scatter to the
surgeons, the reality is not published by the leading centres. A recent brain and surrounding tissues. Losa et al. reported that Gamma Knife
analysis of the UK national acromegaly registry reported that, overall, radiotherapy given to 83 patients following debulking surgery resulted
56% of patients with a microadenoma achieved remission (GH in an 85% remission rate at 10 years post-surgery, with only 10% of
<5mU/l); however, the rates varied between centres from 20 to 68%.
4
patients developing hypopituitarism.
8
Further long-term safety data
As well as the compelling evidence that complication rates are lower are required, but the method appears to be faster-acting at both
with experienced surgeons,
5
this means it is critical that optimal lowering GH and causing hypopituitarism.
© TOUCH BRIEFINGS 2009 51